The goal of this project is to develop a new technology for the detection and analysis of biomolecules based on novel photocleavable linkers (PC-linkers), photocleavable-markers (PC-markers) and matrix assisted laser desorption mass spectrometry (MALDI-MS). AmberGen, Inc. has demonstrated that biomolecules can be captured on a surface using PC-linkers and then photreleased and detected using MALDI-MS. Biomolecules can also be detected with high sensitivity by MALDI-MS using probes which contain PC- markers. PC-linkers and PC-markers are introduced into biomolecules using proprietary reagents developed by AmberGen, Inc. Examples include PC-phosphoramidites for 5'-end labeling of an oligonucleotide during solid-support synthesis and PC-NHS-esters for labeling of proteins and polypeptides. During Phase I this new technology will be evaluated by incorporating PC-linkers and PC-markers into a variety of biomolecules including nucleic acids, proteins and polypeptides and analyzing these molecules by MALDI-MS. Substrates containing uniform and microfabricated 2-D patterned arrays of biomolecules containing PC-linkers and PC-markers will be produced and evaluated using MALDI-MS. PC-linkers and PC-markers combined with MALDI-MS have numerous applications for molecular diagnosis such as DNA analysis, nascent protein analysis and drug screening.